freezing points, or thermal hysteresis, indi-cates that the
mechanism of antifreeze ac-tivity is a noncolligative one,
according to Yin Yeh, professor of applied science, and Robert E.
Feeney, emeritus professor, at the University of California, Davis
[Chern. Rev., 96, 601 (1996)].
The term "antifreeze" should only be applied to proteins that
function noncol-ligativelythat is, do not affect the melt-ing
point, Feeney tells C&EN. The syn-thesis reported by Nishimura
and Tsuda "looks good," and the size of the AFGP "looks okay," he
says. "But more data are needed on freezing and melting."
The Japanese team points out that little evidence has been
reported that can pro-vide a complete explanation of antifreeze
activity. Davies agrees. "Antifreezes like AFGP are thought to work
by an adsorp-tion-inhibition mechanism; that is, they bind to the
surface of ice and inhibit its growth," he says. "The part of the
mechanism that is least understood is the binding part."
The AFGP synthesized by Tsuda and Nishimura is a useful size for
investigating the mechanism of antifreeze activity, sug-gests
Davies. "One potential application of facilitated glycopeptide
synthesis would be to test the binding model by varying the
disaccharide moiety," he says. Howev-er, this will require that the
synthesis can be easily adapted to incorporate different sugars, he
notes.
Nishimura is confident this will be possible. "We can design a
variety of anti-freeze glycoprotein analogs by varying both the
peptide sequence and the car-bohydrate structures in order to
investi-gate the mechanism of antifreeze activity by natural
glycoproteins."
The versatility of the synthetic strategy could also lead to
other applications, ac-cording to Nishimura. The synthetic con-cept
can be applied not only to the synthe-ses of natural antifreeze
glycoproteins, but to the design of glycoclusters, with regulat-ed
distances between the sugar ligands, that are important in other
biological systems.^
Microgravity research looking up Intriguing results from
laboratory experi-ments conducted in the ultra-low-gravity
environment of space were presented at a conference last month that
focused on two recent space shuttle missions. Speak-ers at the
conferenceheld at the Nation-al Academy of Sciences in Washington,
D.C.discussed insights gained into fluid
physics, materials science, combustion sci-ence, protein
crystallization, and other re-search areas when experiments aren't
in-fluenced by gravity.
The experiments were conducted in fall 1995 on the U.S.
Microgravity Labora-tory-2 (USML-2) and in spring 1996 on the U.S.
Microgravity Platform-3 (USMP-3). Many were continuations of
earlier space research.
"At the grassroots level, there's a lot of excitement" in
microgravity research, said David M. Klaus, a research faculty
member in aerospace engineering sci-ences at the University of
Colorado, Boul-der, and payload mission operations manager for
BioServe Space Technolo-gies. BioServe, a National Aeronautics
& Space Administration Center for Space Commercialization, is
affiliated with the University of Colorado and Kansas State
University, Manhattan.
Klaus discussed the effect of micro-gravity on brine shrimp,
mammalian cells, viruses, protein crystals, plant seed-lings,
biomaterials, and microorganisms, among other items. "Most
experiments are part of an ongoing study," he noted.
Development of brine shrimp is accel-erated significantly in
space, he said, but the morphology of space- and Earth-hatched
shrimp is similar. The space-hatched shrimp have commercial
poten-tial as models for assessing toxicological effects, he
explained.
Klaus also described space research on osteoblasts (bone-forming
cells) ulti-mately intended to lead to the develop-ment of
pharmaceuticals that would counteract the loss of bone mass in
astro-nauts. Bone tissue produced by chick osteoblasts grown in
space appears to be less dense than that produced by Earth-grown
control cells, he said.
Space shuttle experiments have shown that microgravity inhibits
the development of bone marrow macrophages, the cells that ingest
foreign particles. Macrophages also respond to inflammation by
stimulat-ing B- and T-lymphocytes, the body's de-fense cells. Thus
the findings in space could have applications in immunologi-cal
research and drug development, said Klaus.
Plants produce less ligninthe cellu-lose in their cell wallsin
the absence of gravity. The energy they save could be re-directed
to enhance the production of oth-er desirable metabolites,
explained Klaus. Space-grown plants also produce larger and heavier
starch-storage vesicles "in an attempt to determine up from down,"
ac-cording to Jeffrey D. Smith, a research as-
Crystals ofi-alanine dehydrogenase grown in space (top) and on
Earth (bottom).
sociate at NASA's Ames Research Center, Moffett Field, Calif.
This finding is the "first evidence that plants physically adapt to
a life in space by changing their sensitiv-ity to gravity," Smith
notes.
Protein crystals grown in space often are superior to those
grown on Earth, fa-cilitating structure determination and ra-tional
drug design. But attempts to grow crystals aren't always
successful. For ex-ample, several crystal-growth experi-ments were
ruined by the delays in liftoff of the shuttle carrying USML-2.
Despite the obstacles, a number of ex-periments on USML-2 went
well, accord-ing to protein crystallographer Daniel C. Carter,
president of New Century Phar-maceuticals, Huntsville, Ala. Among
the successes he described were "the high-est diffracting crystal
and the largest crys-tal to date" of a DuPont Merck HIV pro-tease
complexed to a proprietary inhibi-tor, and "the best structure
obtained over three flights" for human antithrom-
MARCH 3, 1997 C&EN 37
s o f t w a r e / d a t a b a s e u p d a t e
bin (a protease inhibitor that controls blood coagulation)
provided by staictur-al biologist Mark R. Wardell at Washington
University, St. Louis. DuPont Merck and Washington University
researchers were among the coinvestigators from eight institutions
that teamed up with Carter on the USML-2 experiments.
Carter cautioned against judging results based on a single
experiment. "An experiment that doesn't fare well on one flight may
be exemplary on another," he said. He noted that space research is
hampered by the long intervals between flights. "Once we didn't get
to fly for 18 months," he said. "When you grow crystals on a daily
basis, that has a big impact."
Experiments on USMP-3 measured density fluctuations in xenon
near its critical point. The behavior of a material at its critical
point is controlled by random fluctuations in density that become
macroscopic near the critical point. On Earth, the weight of a
fluid compresses density so that most of a sample cannot be
maintained at its critical point. In space, however, microgravity
reduces the fluid's weight and widens the critical volume, enabling
researchers to make measurements. Xenon was chosen to model
critical-point behavior because its critical temperature (Tc) of
16.7 C is relatively close to ambient temperature. Understanding
how xenon behaves at its critical point can provide insight into
fluids, glasses, magnets, liquid crystals, and superconductors.
The "Zeno" experiment, which uses a specially built
precision-light-scattering spectrometer to monitor changes in the
turbidity of a sample in a weightless environment and to measure
time correlations in the photons of light scattered, was first
performed in March 1994 on USMP-2. "But we couldn't have known how
to understand the data from that flight without the data from the
[USMP-3] flight," said Robert W. Gammon, a professor of physics at
the Institute for Physical Science & Technology, University of
Maryland, College Park. The scientists were able to calculate
xenon's Tc to within 10 and measure temperature-imposed density
fluctuations to within 100 of xenon's Tc.
Matthew B. Koss, an assistant professor of materials science and
engineering at Rensselaer Polytechnic Institute, Troy, N.Y.,
emphasized the importance of getting results out quickly and
obtaining feedback on other people's work so researchers will know
"which question to pursue" on the next mission. At the conference,
Koss described the effects of microgravity on denditritic patterns
in metal alloys.
Mairin Brennan
^ ISIS 2.1 (MDL Information Systems, pricing available from
company, circle 301), for Windows and Macintosh, is software for
registration, management, retrieval, display, and analysis of
scientific data. This version provides enhanced capabilities for
the representation, storage, and management of polymer information
and also includes chemical representation enhancements.
Scientific products (VWR Scientific Products, circle 302) can
now be ordered direct over the web at http:// www.vwrsp.com. The
company markets laboratory chemicals, equipment, and supplies.
ChemPrep (Institute for Scientific Information, subscription
price available from vendor, circle 303), a reaction database on
CD-ROM, is searchable by substructure, transformation, or text.
Data are available on over 300,000 reactions from 1986 to the
present, and the database will be updated quarterly. ChemPrep runs
under Windows 3.1.
^ Chart of the Nuclides: A Tutorial (Physics Academic Software,
$100, circle 304), for Macintosh II or later computers, helps
students learn how to read and understand data presented in a
standard chart of nuclides.
^ TRC Thermophysical Databank (Technical Database Services,
pricing available from company, circle 305) provides evaluated
chemical engineering data on thermodynamic, thermo-chemical, and
transport properties of approximately 10,000 organic and
non-metallic inorganic compounds and their binary and ternary
mixtures. Currently, data may be obtained by submitting search
requests via the Internet, phone, or fax, but the company plans to
provide direct public access to the file in the fourth quarter of
1997.
^ Chem-X/Inventory (Chemical Design, price available from
company, circle 306) is a module of the molecular-modeling program
Chem-X that manages reagent and screening-compound databases for
combinatorial chemistry applications. It runs on a variety of
platforms, ranging from PCs and Macintoshes to client-server
systems.
^ Accord for Excel 2.5 (Synopsys Scientific Systems; $695, $175
upgrade,
40% discount to academics and students; circle 307), for the
Power Macintosh and Windows 3.1, 95, and NT computers, provides a
range of facilities to manage, analyze, and search chemical
"objects" and associated data within the Microsoft Excel
spreadsheet environment. Enhancements in this version include
faster chemical table operations and stereochemical searching.
Accord Chemistry Viewer (Synopsys Scientific Systems, free,
circle 308) for the Power Macintosh can be freely downloaded from
Synopsys' web site (http://www.synopsys.co.uk/) for personal,
academic, and registered corporate use. Installed as a helper
application for web-browsers, it enables users to display chemical
strucaires and reactions downloaded from the web in a variety of
chemical formatsincluding Accord, SMILES strings, ChemDraw files,
Molfiles, and Rxnfiles. It also makes it possible to display
structures received as MIME attachments to e-mail messages. The
viewer is also available for Windows 3.1, 95, and NT.
DMCplus (Aspen Technology, typical single-use license $70,000,
circle 309) is a multivariable process controller for Windows 95
and NT and a variety of Digital, UNIX, and IBM systems. Process
engineers use DMCplus to model, predict, and control process
manufacturing.
^ FactorySuite and FactorySuite Plus (Wonderware; $9,950 and
$12,500, respectively; circle 310) are industrial automation
programs for Windows NT. FactorySuite provides process
visualization, PC-based machine and process control, real-time
plant data management, Internet/ intranet viewing, and factory
equipment interfacing. The Plus program adds work-in-progress
tracking and production and batch management.
^ Chemkey Search (Heterodata, $475 single user, circle 311) is a
database of 50,000 references from organic chemistry journals with
an emphasis on synthetic methodology, asymmetric synthesis,
stereochemistry, and heterocyclic and organometallic chemistry. A
Macintosh- and PC-based program, it is updated yearly.
^ For information on these items, see Reader Service Card
38 MARCH 3, 1997 C&EN
science
http://http://www.vwrsp.comhttp://www.synopsys.co.uk/
Microgravity research looking up
